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Effect of clozapine on neuropsychological test performance in patients with schizophrenia
Abstracts from the 18th Annual Meeting
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H I V - / " a t risk" control subjects were administered the CVLT at four assessments. A 2-week period separated the first and second assessments and 6 months separated other assessments. Trend analyses conducted across all four assessments indicate: (1) as expected, practice effects were noted between assessments one and two, and (2) practice effects were minimized at assessments three and four. Results suggest that researchers and clinicians may consider using a dual baseline assessment approach to minimize the practice effects in serial assessment studies. Future investigations with other instruments and other populations are advised.
Lewandowski, A., Francom, S., Reeves. D., & Cole, J. Neuropsychologica/ Methodology for Repeated Testing Under Clinical Trial Conditions'. Recently there has been a growing interest in the application of neuropsychological methodology in human pharmaceutical research. This presentation details the specific methodological considerations in a drug efficacy study using a highly flexible computerbased neuropsychological instrument in human pharmaceutical research. Serial neuropsychological testing was administered over 30 times with the Automated Neuropsychological Assessment Metrics (ANAM) with eight healthy male subjects ranging in age from 18 to 40 years using a two-way crossover design during two inpatient stays of 38 hours each, separated by 7 days. The study focused on establishing the primary methodology and utility for using ANAM for repeated measures assessment in human (Phase lI and III) clinical trials. Experimental conditions included, physical examination, drug administration, vital signs, EEG, ECG, and blood and urine collection (CBC, EMITA). A drug dose was administered in the morning and after an overnight fast, with vital signs recorded at predetermined pre and post-dose intervals. Neuropsychological testing was conducted at - 1 hour and -30 minutes pre-dose, and 2, 4, 6, 8, and 12 hours post-dose, and included mood, arousal, reaction time, simple and sustained attention and concentration, learning, memory, mathematical reasoning, spatial processing, and visual-spatial tracking. Statistical findings outline the detailed data analysis available with repeated measures methodology. Findings support the use of ANAM as a valid, practical, reliable, stable and cost-effective instrument for quickly detecting subtle changes in emotions and cognitive efficiency in the pharmaceutical evaluation of CNS drugs during clinical trial conditions. The limitations of conventional normative-based neuropsychological measures are discussed along with applications in clinical practice.
PSYCHIATRIC ILLNESS Battle, Y. L., Evans, C. C., Miller, S. E., Evans, D. R., Mahadik, S. P., Miller, L. S., & Wilkens, J. V. Effect of Clozapine on Neuropsychological Test Performance in Patients with Schizophrenia. Previous studies have suggested that clozapine, an atypical ant/psychotic, has superior efficacy to typical neuroleptics in improving psychiatric symptoms and reducing extrapyramidal side effects in patients with schizophrenia. However, contradictory findings have been reported regarding clozapine's efficacy in improving neuropsychological test performance. The present study was designed to examine the comparative efficacy of clozapine versus typical neuroleptic medications on cognitive functioning. Neuropsychological measures of motor functioning, attention, executive function, memory, fluency, and visual-spatial ability were administered to 27 schizophrenic medical center patients
112
Abstracts from the 18th Annual Meeting
receiving maintenance doses of either clozapine (n = 16) or typical neuroleptic medication (n = 11). There were no differences between the two groups in age, sex, education, onset and length of illness, or handedness. There were also no between group differences with regard to positive and negative symptoms, as measured by the Brief Psychiatric Rating Scale. Medication dosage was controlled for in all analyses. Using Analysis of Covariance procedures, clozapine patients outperformed typical neuroleptic patients on tasks of fine motor speed (Finger Tapping--right hand; p < .01; left hand; p < .001) and fine motor coordination (Grooved Pegboard--right hand; p = .07; left hand; p < .001). No significant between-group differences were found on any of the other cognitive measures. These findings suggest that clozapine has less impact on motor functioning than typical neuroleptic medications in patients with schizophrenia.
Berns, S., Jaeger, J., Panopoulus, S., & Farella-Busch, S. Neuropsychological Deficits and Functional Disability in Patients with Schizophrenia. Schizophrenia is a chronic and persistent mental illness associated with reduced independent functioning (IF) manifested by impairment in the ability to work, go to school, engage in social relationships, and live independently. While psychopathological symptoms such as delusions and hallucinations are the hallmark of schizophrenia and the target of psychotherapeutic and rehabilitation efforts, there is little demonstrated relationship between symptoms and IF. Rehabilitation programs and pharmacological treatments have been only minimally successful in improving independent functioning (IF). The prevalence of neuropsychological (NP) impairment in schizophrenia has been well established, however, their functional consequences are largely unknown. Several recent studies suggest that neuropsychologieal deficits contribute to functional disability apart from the effects of psychopathology (PP). This study used a multidimensional approach to examine the relationships between domains of NP functioning (including memory, attention, executive, motor and language), psychopathology (Brief Psychiatric Rating Scale Factors) and types of functional disability (including vocational, social, and residential). Sixty patients with schizophrenia, age 18 to 45, were administered a set of NP tests, psychopathology ratings, and IF measures. Cross-sectional analyses indicate NP functioning (particularly in the attention domain) is related to vocational disability while psychopathology (particularly anergia and thought disturbance) was related to social disability. Analyses of the relationship between current NP performance, PP ratings and history of functional disability suggest that both executive functioning and psychopathology are related to different aspects of past productive activity. No relationship was found between NP performance and PP ratings. Thus, NP functioning and psychopathology reflect independent contributors to functional disability. Identification of the specific correlates of different types of functional disability would provide a guide for the development of more effective interventions.
Elliott, T., Richards, V., Ambler, C., Miller, D., Holker, E., Gwin, R., Lengenfeider, J., & Thomas, T. Neuropsychological Functioning of Women with Borderline Personality Disorder. Recent studies have suggested possible neuropsychological impairments among women with Borderline Personality Disorder (BPD). However, results have not been consistent, and have not always controlled for the influence of depression and substance abuse. Therefore the present study administered the Structured Clinical Interview for DSMIII-R (SCID) to a random sample of detoxified women drawn from a rehabilitation center in order to identify women who qualified for both BPD and substance abuse/dependence (N = 19) or substance-abuse/dependence but not BPD (N = 23). As the BPD
l 11
H I V - / " a t risk" control subjects were administered the CVLT at four assessments. A 2-week period separated the first and second assessments and 6 months separated other assessments. Trend analyses conducted across all four assessments indicate: (1) as expected, practice effects were noted between assessments one and two, and (2) practice effects were minimized at assessments three and four. Results suggest that researchers and clinicians may consider using a dual baseline assessment approach to minimize the practice effects in serial assessment studies. Future investigations with other instruments and other populations are advised.
Lewandowski, A., Francom, S., Reeves. D., & Cole, J. Neuropsychologica/ Methodology for Repeated Testing Under Clinical Trial Conditions'. Recently there has been a growing interest in the application of neuropsychological methodology in human pharmaceutical research. This presentation details the specific methodological considerations in a drug efficacy study using a highly flexible computerbased neuropsychological instrument in human pharmaceutical research. Serial neuropsychological testing was administered over 30 times with the Automated Neuropsychological Assessment Metrics (ANAM) with eight healthy male subjects ranging in age from 18 to 40 years using a two-way crossover design during two inpatient stays of 38 hours each, separated by 7 days. The study focused on establishing the primary methodology and utility for using ANAM for repeated measures assessment in human (Phase lI and III) clinical trials. Experimental conditions included, physical examination, drug administration, vital signs, EEG, ECG, and blood and urine collection (CBC, EMITA). A drug dose was administered in the morning and after an overnight fast, with vital signs recorded at predetermined pre and post-dose intervals. Neuropsychological testing was conducted at - 1 hour and -30 minutes pre-dose, and 2, 4, 6, 8, and 12 hours post-dose, and included mood, arousal, reaction time, simple and sustained attention and concentration, learning, memory, mathematical reasoning, spatial processing, and visual-spatial tracking. Statistical findings outline the detailed data analysis available with repeated measures methodology. Findings support the use of ANAM as a valid, practical, reliable, stable and cost-effective instrument for quickly detecting subtle changes in emotions and cognitive efficiency in the pharmaceutical evaluation of CNS drugs during clinical trial conditions. The limitations of conventional normative-based neuropsychological measures are discussed along with applications in clinical practice.
PSYCHIATRIC ILLNESS Battle, Y. L., Evans, C. C., Miller, S. E., Evans, D. R., Mahadik, S. P., Miller, L. S., & Wilkens, J. V. Effect of Clozapine on Neuropsychological Test Performance in Patients with Schizophrenia. Previous studies have suggested that clozapine, an atypical ant/psychotic, has superior efficacy to typical neuroleptics in improving psychiatric symptoms and reducing extrapyramidal side effects in patients with schizophrenia. However, contradictory findings have been reported regarding clozapine's efficacy in improving neuropsychological test performance. The present study was designed to examine the comparative efficacy of clozapine versus typical neuroleptic medications on cognitive functioning. Neuropsychological measures of motor functioning, attention, executive function, memory, fluency, and visual-spatial ability were administered to 27 schizophrenic medical center patients
112
Abstracts from the 18th Annual Meeting
receiving maintenance doses of either clozapine (n = 16) or typical neuroleptic medication (n = 11). There were no differences between the two groups in age, sex, education, onset and length of illness, or handedness. There were also no between group differences with regard to positive and negative symptoms, as measured by the Brief Psychiatric Rating Scale. Medication dosage was controlled for in all analyses. Using Analysis of Covariance procedures, clozapine patients outperformed typical neuroleptic patients on tasks of fine motor speed (Finger Tapping--right hand; p < .01; left hand; p < .001) and fine motor coordination (Grooved Pegboard--right hand; p = .07; left hand; p < .001). No significant between-group differences were found on any of the other cognitive measures. These findings suggest that clozapine has less impact on motor functioning than typical neuroleptic medications in patients with schizophrenia.
Berns, S., Jaeger, J., Panopoulus, S., & Farella-Busch, S. Neuropsychological Deficits and Functional Disability in Patients with Schizophrenia. Schizophrenia is a chronic and persistent mental illness associated with reduced independent functioning (IF) manifested by impairment in the ability to work, go to school, engage in social relationships, and live independently. While psychopathological symptoms such as delusions and hallucinations are the hallmark of schizophrenia and the target of psychotherapeutic and rehabilitation efforts, there is little demonstrated relationship between symptoms and IF. Rehabilitation programs and pharmacological treatments have been only minimally successful in improving independent functioning (IF). The prevalence of neuropsychological (NP) impairment in schizophrenia has been well established, however, their functional consequences are largely unknown. Several recent studies suggest that neuropsychologieal deficits contribute to functional disability apart from the effects of psychopathology (PP). This study used a multidimensional approach to examine the relationships between domains of NP functioning (including memory, attention, executive, motor and language), psychopathology (Brief Psychiatric Rating Scale Factors) and types of functional disability (including vocational, social, and residential). Sixty patients with schizophrenia, age 18 to 45, were administered a set of NP tests, psychopathology ratings, and IF measures. Cross-sectional analyses indicate NP functioning (particularly in the attention domain) is related to vocational disability while psychopathology (particularly anergia and thought disturbance) was related to social disability. Analyses of the relationship between current NP performance, PP ratings and history of functional disability suggest that both executive functioning and psychopathology are related to different aspects of past productive activity. No relationship was found between NP performance and PP ratings. Thus, NP functioning and psychopathology reflect independent contributors to functional disability. Identification of the specific correlates of different types of functional disability would provide a guide for the development of more effective interventions.
Elliott, T., Richards, V., Ambler, C., Miller, D., Holker, E., Gwin, R., Lengenfeider, J., & Thomas, T. Neuropsychological Functioning of Women with Borderline Personality Disorder. Recent studies have suggested possible neuropsychological impairments among women with Borderline Personality Disorder (BPD). However, results have not been consistent, and have not always controlled for the influence of depression and substance abuse. Therefore the present study administered the Structured Clinical Interview for DSMIII-R (SCID) to a random sample of detoxified women drawn from a rehabilitation center in order to identify women who qualified for both BPD and substance abuse/dependence (N = 19) or substance-abuse/dependence but not BPD (N = 23). As the BPD